Oscar D. Bruno

Cabergoline monotherapy in the long-term treatment of Cushing's disease

BACKGROUND Cabergoline is a long-acting dopamine receptor agonist used to treat prolactinomas. Identification of D(2) receptors in corticotroph tumors led to clinical trials of cabergoline therapy in limited cases of Nelsons syndrome, ectopic ACTH-secreting tumors, and recently Cushings disease (CD). OBJECTIVE To evaluate the long-term efficacy of cabergoline monotherapy in patients with CD. METHODS Retrospective analysis of non-randomized clinical therapy with cabergoline in 30 patients with CD treated in academic centers of Buenos Aires and Montreal. Cabergoline was initiated at 0.5-1.0 mg/week and adjusted up to a maximal dose of 6 mg/week based on urinary free cortisol (UFC) levels. Complete response to cabergoline was defined as a sustained normalization of UFC with at least two normal values measured at 1-3 months interval; partial response was defined as a decrease of UFC to <125% of the upper limit of normal, and treatment failure as UFC ≥ 125% of it. RESULTS Within 3-6 months, complete response was achieved in 11 patients (36.6%) and partial response in 4 patients (13.3%). After long-term therapy, nine patients (30%) remain with a complete response after a mean of 37 months (range from 12 to 60 months) with a mean dose of 2.1 mg/week of cabergoline. Two patients escaped after 2 and 5 years of complete response, but one patient transiently renormalized UFC after an increase in cabergoline dosage. No long-term response was maintained in four initial partial responders. CONCLUSIONS Cabergoline monotherapy can provide an effective long-term medical therapy for selected patients with CD, but requires close follow-up for dose adjustments.

Temozolomide Therapy for Aggressive Pituitary Tumors: Results in a Small Series of Patients from Argentina

We evaluated results of temozolomide (TMZ) therapy in six patients, aged 34–78 years, presenting aggressive pituitary tumors. In all the patients tested O6-methylguanine-DNA methyltransferase (MGMT) immunoexpression in surgical specimens was absent. Patients received temozolomide 140–320 mg/day for 5 days monthly for at least 3 months. In two patients minimum time for evaluation could not be reached because of death in a 76-year-old man with a malignant prolactinoma and of severe neutro-thrombopenia in a 47-year-old woman with nonfunctioning pituitary adenoma. In two patients (a 34-year-old acromegalic woman and a 39-year-old woman with Nelsons syndrome) no response was observed after 4 and 6 months, respectively, and the treatment was stopped. Conversely, two 52- and 42-year-old women with Cushings disease had long-term total clinical and radiological remissions which persisted after stopping temozolomide. We conclude that TMZ therapy may be of variable efficacy depending on—until now—incompletely understood factors. Cooperative work on a greater number of cases of aggressive pituitary tumors should be crucial to establish the indications, doses, and duration of temozolomide administration.

LONG-TERM MANAGEMENT WITH OCTREOTIDE OR CABERGOLINE IN ECTOPIC CORTICOTROPIN HYPERSECRETION: CASE REPORT AND LITERATURE REVIEW

OBJECTIVE To describe the corticotropin response to long-term octreotide or cabergoline administration in a patient with ectopic corticotropin secretion who underwent adrenalectomy. METHODS We describe the clinical, radiologic, and biochemical findings of the study patient over the course of 18 years. RESULTS A 40-year-old woman was evaluated for Cushing syndrome. On the basis of biochemical indices, Cushing disease was diagnosed and pituitary exploration was performed. No cure was achieved. Computed tomography of the chest revealed a right lung nodule due to a lung carcinoid tumor that was then surgically excised. Because of persistent hypercortisolism, total adrenalectomy was performed. Subsequently, corticotropin levels rose dramatically and hyperpigmentation developed while serum cortisol was in the reference range. The patient was treated with octreotide for 3 years and then with cabergoline for 8 years. While taking octreotide, corticotropin values decreased, accompanied by depigmentation and development of signs of adrenal insufficiency, which led to the reinstitution of supplemental hydrocortisone. Cabergoline induced a similar long-lasting effect on the clinical and biochemical parameters observed. Eight years later, she is still treated with cabergoline, and no lung tumor has been detected. CONCLUSIONS In this patient with ectopic Cushing syndrome, treatment with either octreotide or cabergoline markedly reduced corticotropin levels and hyperpigmentation.

Transport of cortisol, progesterone and cholesterol across isolated mesentery. Effect of metyrapone.

SummaryIsolated rat mesentery, mounted in a diffusion cell, is used as a model for the study of vascular endothelium permeability characteristics. The passage of tracer molecules is measured in the absence of osmotic or hydrostatic pressure gradients across the mesentery. The permeability coefficient of the membrane for cortisol and progesterone is similar. When bound to transcortin, cortisol crosses mesentery at a significantly slower rate. Metyrapone diatartrate increases by 30% the passage of free and of transcortinbound cortisol, but is without effect on the passage of progesterone or glucose in the same conditions. When the transfer of cholesterol across mesentery is studied, a high percentage of the tracer is trapped by the membrane.

Long‐lasting complete remission after therapy with temozolomide in two patients with macrocorticotropinoma causing Cushing's disease

the dimension of sexual activity, as compared with those without such history, and thus, this subgroup of patients with CHH may be those at greatest risk for sexual health problems later in life. In conclusion, our results show that male patients with CHH have impaired HRQoL compared to the age-standardized general male population, particularly on dimensions associated with psychological well-being. Late diagnosis and delayed start of HRT may have a lasting adverse influence on HRQoL. Our findings support inclusion of screening for depression and anxiety disorders to the regular medical follow-up of patients with CHH.

FSH-Producing Pituitary Macroadenoma: Report of 2 Cases with Clinical Manifestations of Hormone Excess

ABSTRACT Objective: Gonadotropinomas with signs related to hypergonadotropinemia have been rarely published. We report 2 clinical cases of follicle-stimulating hormone (FSH)-producing macroadenomas showing manifestations of hormone hypersecretion. Methods: The clinical, laboratory, and imaging findings are presented with a review of the literature. Results: A 51-year-old man was admitted to the hospital because of cranioencephalic trauma following seizures. He reported previous altered behavior, depression, sphincter incontinence, and visual troubles. Physical examination revealed signs of hypogonadism and increased bilateral testicular volume. Magnetic resonance imaging (MRI) showed a large lesion in the sellar-suprasellar area, with mass effect. Hormone testing showed high levels of FSH (517 mIU/mL) and low levels of both luteinizing hormone (LH) (2.2 mIU/mL) and testosterone (1.3 ng/mL). A partial resection of an immunopositive FSH adenoma was performed; FSH declined after surgery, but the patient died...